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71.
Jun-Hyuk Choi So-Young Kim Sook-Kyung Kim Michael G. Kemp Aziz Sancar 《The Journal of biological chemistry》2015,290(48):28812-28821
DNA damage by UV and UV-mimetic agents elicits a set of inter-related responses in mammalian cells, including DNA repair, DNA damage checkpoints, and apoptosis. Conventionally, these responses are analyzed separately using different methodologies. Here we describe a unified approach that is capable of quantifying all three responses in parallel using lysates from the same population of cells. We show that a highly sensitive in vivo excision repair assay is capable of detecting nucleotide excision repair of a wide spectrum of DNA lesions (UV damage, chemical carcinogens, and chemotherapeutic drugs) within minutes of damage induction. This method therefore allows for a real-time measure of nucleotide excision repair activity that can be monitored in conjunction with other components of the DNA damage response, including DNA damage checkpoint and apoptotic signaling. This approach therefore provides a convenient and reliable platform for simultaneously examining multiple aspects of the DNA damage response in a single population of cells that can be applied for a diverse array of carcinogenic and chemotherapeutic agents. 相似文献
72.
Kyong-Rock Do Young-Seok Cho Hyung-Keun Kim Byung-Hee Hwang Eun-Jung Shin Hae-Bin Jeong Sung-Soo Kim Hiun-Suk Chae Myung-Gyu Choi 《The Korean journal of parasitology》2010,48(1):75-78
The present study investigated characteristics of 24 parasite infection cases detected during colonoscopy in a regional hospital from January 2001 to December 2008. Sixteen patients were confirmed with Trichuris trichiura infection, 6 patients were with Ascaris lumbricoides infection, 1 patient with Enterobius vermicularis infection, and 1 patient with Anisakis infection. Among them, 7 patients (43.8%) were asymptomatic. Colonoscopy findings were normal in 18 patients (75.0%). Among the patients with T. trichiura infection, colonoscopy showed several erosions in 2 patients (8.3%) and non-specific inflammation of the affected segment of the colon in 3 patients (12.5%). In 1 patient with anisakiasis, colonoscopy revealed a markedly swollen colonic wall. Stool examinations were performed before treatment in 7 patients (29.2%) and were all negative for parasite eggs or worms. These results suggest that colonoscopy is a useful diagnostic approach for parasitic infections even for asymptomatic patients and for patients with negative stool examinations. 相似文献
73.
Bo-Hwa Choi Souvik Chattopadhaya Le Nguyen Thanh Lin Feng Quoc Toan Nguyen Chuan Bian Lim Amaravadhi Harikishore Ravi Prakash Reddy Nanga Nagakumar Bharatham Yan Zhao Xuewei Liu Ho Sup Yoon 《PloS one》2014,9(10)
Microtubules are a highly validated target in cancer therapy. However, the clinical development of tubulin binding agents (TBA) has been hampered by toxicity and chemoresistance issues and has necessitated the search for new TBAs. Here, we report the identification of a novel cell permeable, tubulin-destabilizing molecule - 4,5,6,7-tetrahydro-1H-indazole-3-carboxylic acid [1p-tolyl-meth-(E)-ylidene]-hydrazide (termed as Suprafenacine, SRF). SRF, identified by in silico screening of annotated chemical libraries, was shown to bind microtubules at the colchicine-binding site and inhibit polymerization. This led to G2/M cell cycle arrest and cell death via a mitochondria-mediated apoptotic pathway. Cell death was preceded by loss of mitochondrial membrane potential, JNK - mediated phosphorylation of Bcl-2 and Bad, and activation of caspase-3. Intriguingly, SRF was found to selectively inhibit cancer cell proliferation and was effective against drug-resistant cancer cells by virtue of its ability to bypass the multidrug resistance transporter P-glycoprotein. Taken together, our results suggest that SRF has potential as a chemotherapeutic agent for cancer treatment and provides an alternate scaffold for the development of improved anti-cancer agents. 相似文献
74.
75.
76.
TopBP1, acting in concert with DNA containing bulky base lesions, stimulates ATR kinase activity under physiologically relevant reaction conditions. Here, we analyze the roles of the three components in ATR activation: DNA, base damage and TopBP1. We show that base adducts caused by a potent carcinogen, benzo[a]pyrene diol epoxide (BPDE), constitute a strong signal for TopBP1-dependent ATR kinase activity on Chk1 and p53. We find that the C-terminus of TopBP1 binds preferentially to damaged DNA and is sufficient to mediate damaged DNA-dependent ATR activation in a manner similar to full-length TopBP1. Significantly, we find that stimulation of ATR by BPDE-damaged DNA exhibits strong dependence on the length of DNA, with essentially no stimulation with fragments of 0.2 kb and reaching maximum stimulation with 2 kb fragments. Moreover, TopBP1 shows preferential binding to longer DNA fragments and, in contrast to previous biochemical studies, TopBP1 binding is completely independent of DNA ends. We find that TopBP1 binds to circular and linear DNAs with comparable affinities and that these DNA forms elicit the same level of TopBP1-dependent ATR activation. Taken together, these findings suggest a cooperative activation mechanism for the ATR checkpoint kinase by TopBP1 and damaged DNA. 相似文献
77.
Several patterns of feeding behaviors have been documented in benthophagous fishes. The foraging behavior of the maiden goby,
Pterogobius virgo, was studied at Kurahashi Island in the Seto Inland Sea, Japan. Pterogobius virgo foraged mostly on polychaetes by volume from among several available prey items by digging in the sandy bottom. The digging
behavior comprised swing of only pectoral fins or of both pectoral fins and body. Pectoral fin swing exposed the cryptic prey
within the bottom, and fins and body swing exposed the prey and washed the sediment away. The swings were repeatedly and continuously
conducted at a site during the daytime, making a pit several centimeters deep in which the fish was located. After the prey
was exposed, the fish immediately and rapidly picked up the prey. Polychaetes were abundant prey in the sediment, occurring
in the layer 3–5 cm deep from the bottom surface in the study area. In this goby, spot-fixed fin digging, the first documentation
of feeding habits in gobies, may be effective for feeding on the most valuable prey, i.e., polychaetes, which may be otherwise
unavailable for this fish.
Received: April 24, 2001 / Revised: April 26, 2002 / Accepted: May 7, 2002 相似文献
78.
Estrone sulfate sulfohydrolase (estrogen sulfatase) activity was solubilized by treatment with Triton X-100 from 105,000 g pellets of guinea pig uterus, testis and brain, as well as from rat liver and human placenta. The solubilized forms were subjected to chromatofocusing in the fast protein liquid chromatography (FPLC) system and on conventional columns packed in our laboratory. The guinea pig tissue pattern was complex. Uterus showed peaks of activity with apparent pI's of 9.11 and 7.6; testis contained 3 peaks with pI's of 9.18, 8.7 and 7.5; brain possessed peaks with pI's of 9.28 and 8.6. In each case the major activity peak was that with pI greater than 9. Rat liver activity chromatofocused as a single peak of apparent pI = 6.87 and the human placental enzyme also showed a single, though broad, peak, of pI = 6.57. This suggests not only that the guinea pig enzyme(s) differs markedly from those of rat liver and human placenta, but that there may be qualitative differences between the forms in the three guinea pig tissues. Chromatofocusing behaviour was not independent of the specific exchange resins and ampholytes utilized. The recovered enzyme activity was fairly stable and it seems that chromatofocusing could be a useful step in purification of the guinea pig enzyme(s), particularly the main form possessing a pI greater than 9. 相似文献
79.
Previous research showed that addition of nutrient nitrogen to ligninolytic (stationary, nitrogen-starved) cultures of the wood-decomposing basidiomycete Phanerochaete chrysosporium causes a suppression of lignin degradation. The present study examined early effects on nitrogen metabolism that followed addition of NH
4
+
and l-glutamate at concentrations that yield similar patterns of suppression. Both nitrogenous compounds were rapidly assimilated (>80% in 6 h). Both caused an initial 80% or greater increase in the intracellular glutamate pool and had similar effects in increasing the specific activities of NADP- and NAD-glutamate dehydrogenases and glutamine synthetase. Differences between the effects of added NH
4
+
and glutamate showed that suppression was not correlated with intracellular pools of arginine or glutamine, nor was the maintenance of an elevated glutamate pool required to maintain the suppressed state. While a portion of the initial glutamate suppression could be attributed to an effect on central carbon metabolism through glutamate catabolism by NAD-glutamate dehydrogenase, the long term suppression by glutamate and the suppression by NH
4
+
were more specific. Suppression by NH
4
+
or glutamate in the presence or absence of protein synthesis (cycloheximide) followed essentially identical kinetics during 12 h. These results indicate that nitrogen additions cause a biochemical repression of enzymes associated with lignin degradation. Results are consistent with the hypothesis that nitrogen metabolism via glutamate plays a role in initiation of repression.Non-Standard Abbreviations DMS
2,2-dimethylsuccinate
- TCA
trichloroacetic acid 相似文献
80.
This study examined the effect of dietary polyunsaturated fatty acids (PUFA) that were supplemented with vitamin E on lipid peroxidation, glutathione-dependent detoxifying enzyme system activity, and lipogenic fatty acid synthase (FAS) expression in rat liver. Male Sprague-Dawley rats were fed semipurified diets containing either 1% (w/w) corn oil or 10% each of beef tallow, corn oil, perilla oil, and fish oil for 4 wk. Alpha-tocopherol was supplemented in perilla oil (0.015%) and fish oil (0.019%). Hepatic thiobarbituric acid reactive substances, an estimate of lipid peroxidation, were not significantly different among the dietary groups. The glutathione peroxidase, glutathione reductase, and glutathione S-transferase activities were all elevated by the polyunsaturated fats, especially fish oil. The activity of FAS was reduced in the polyunsaturated fat-fed groups in the order of fish oil, perilla oil, and corn oil. The mRNA contents decreased in rats that were fed the 10% fat diets, particularly polyunsaturated fats, compared with the rats that were fed the 1% corn oil diet. Similarly, the inhibitory effect was the greatest in fish oil. These results suggest that lipid peroxidation can be minimized by vitamin E; PUFA in itself has a suppressive effect on lipogenic enzyme. 相似文献